Prospective analysis of sera from patients with inoperable bronchogenic carcinoma reveals an incidence of @ 6% ectopic placental protein production. Ectopic production of the alpha subunit in patients with malignant carcinoid tumors and of alpha and/or hCG in patients with islet cell carcinomas has been documented. Almost 25% of a retrospective series of 62 sera from patients with testis carcinoma contained ectopic hCG or hPL. Biochemical marker (hCG, alpha subunit) and clinical response were concordant in 7/9 assessible chemotherapy periods in 4 patients with inoperable carcinoma and ectopic placental protein production. A clonal cell strain (ChaGo-Kl) derived from a bronchogenic carcinoma secreted alpha subunit in large amounts but far less, if any, hCG-beta or complete hCG. Alpha production by this clone exceeded hCG production by a choriocarcinoma clone grown under identical conditions. Cell lines established from normal human placenta also secrete large amounts of alpha but little complete hCG. Heterogeneity already documented for ectopic alpha has been found in circulating ectopic hCG and ectopic hPL. For the last mentioned, studies with placental mRNA suggest a possible in vitro counterpart.